Increased urinary level of oxidized nucleosides in patients with mild-to-moderate Alzheimerʹs disease

Objective: Oxidative stress may play an important role in the pathogenesis of Alzheimerʹs disease (AD). Design and methods: To investigate the possible role of oxidative DNA damage in the pathogenesis of AD, we measured the metabolite concentrations of oxidized nucleosides (pseudouridine, 1-methyladenosine, 5-methylcytidine, 5-methyl-2′-deoxycytidine, 3-methyluridine, N2, N2-dimethylguanosine, 8-hydroxy-2′-deoxyguanosine, 5-deoxyadenosine and 2-deoxyguanosine) in urine between AD (n = 36) and control subjects (n = 34) using liquid chromatography-mass spectrometry (LC-MS) without urine preparation. Results: In AD, the 3-methyluridine, 1-methyladenosine, 8-hydroxy-2′-deoxyguanosine (p < 0.05, respectively), 2-deoxyguanosine (p < 0.01) and pseudouridine, N2, N2-dimethylguanosine (p < 0.001, respectively) were significantly increased when compared with the control subjects. Conclusion: The results indicate that oxidized urinary nucleosides may be useful as biomarkers for AD in early stages.